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    Research Grants Awarded

    Ductal Carcinoma In Situ and BRCA1/2: Outcomes and Risk Prediction

    Study Section:
    RISK and Prevention, Epidemiology

    Scientific Abstract:
    The role of ductal carcinoma in situ (DCIS) with respect to breast-ovarian cancer syndromes associated with the genes BRCA1 and BRCA2 is unclear. Recent findings indicate that the prevalence of disease-associated mutations in BRCA1/2 among women diagnosed with DCIS is similar to that for women diagnosed with invasive breast cancer. However, the pathologic and clinical characteristics of DCIS (and hence screening and treatment options) for BRCA1/2 carriers relative to non-carriers remains to be defined. Efforts to study this topic are important as 1) there is evidence of a low level of patient and clinician awareness that DCIS may be associated with BRCA1/2 and that, in carriers, standard treatment for DCIS may not be appropriate, 2) preliminary data suggest that DCIS in women with mutations in BRCA1/2 may progress more quickly to invasive breast cancer than for women without such mutations, and 3) up to 20% of screened breast cancer patients are diagnosed with DCIS; hence, in the coming century up to one in fifty women in the United States will likely be diagnosed with this tumor during her lifetime. At present, few women with DCIS have been tested for disease-associated mutations in BRCA1/2 and no single research center includes a sufficient number of patients for study. We propose a multi-center, collaborative effort to construct a sample of approximately 175 female BRCA1/2 carriers diagnosed with DCIS drawn from a population-based case/control study of DCIS as well as from a number of large high-risk cancer clinics across the United States in an effort to define preliminary estimates of outcome for these women. The goals of this application are: 1) To provide annual and five-year cumulative estimates of ipsilateral and contralateral breast cancer risk, as well as risk of ovarian cancer and death for women diagnosed with DCIS and who have mutations in BRCA1/2, 2) To compare these risks with those for women diagnosed with DCIS and who do not carry mutations in BRCA1/2 and those for women not diagnosed with DCIS (controls), 3) To measure and compare the prevalence of pathologic characteristics (estrogen, progesterone, erbB-2, and Ki-67 (MIB-1) receptor positivity as well as tumor size, grade and comedo necrosis) of DCIS diagnosed in women with mutations in BRCA1/2 with those in DCIS patients without such mutations, 4) To present preliminary risk models and clinical guidelines for the management of DCIS in BRCA1/2 mutation carriers.

    Lay Abstract:
    The role of ductal carcinoma in situ (DCIS) with respect to breast-ovarian cancer syndromes associated with the breast/ovarian cancer susceptibility genes BRCA1 and BRCA2 is unclear. Recent data indicate that the prevalence of disease-associated mutations in BRCA1/2 among women diagnosed with DCIS is similar to that for women diagnosed with invasive breast cancer. However, the pathologic and clinical characteristics of DCIS (and hence screening and treatment options) for BRCA1/2 carriers relative to non-carriers remains to be defined. Efforts to study this topic are important as 1) there is evidence of a low level of patient and clinician awareness that DCIS may be associated with BRCA1/2 and that, in carriers, standard treatment for DCIS may not be appropriate, 2) preliminary data suggest that DCIS in women with mutations in BRCA1/2 may progress more quickly to invasive breast cancer than for women without such mutations, and 3) up to 20% of screened breast cancer patients are diagnosed with DCIS; hence, in the coming century up to one in fifty women in the United States will likely be diagnosed with this tumor during her lifetime. At present, few women with DCIS have been tested for disease-associated mutations in BRCA1/2 and no single research center includes a sufficient number of patients for study. We propose a multi-center, collaborative effort to construct a sample of approximately 175 female BRCA1/2 carriers diagnosed with DCIS drawn from both population-based data and high-risk breast/ovarian cancer clinics across the United States in an effort to define preliminary estimates of outcome for these women. The goals of this application are: 1) To provide annual and five-year cumulative estimates of risk for breast and ovarian cancer as well as death for women diagnosed with DCIS and who have mutations in BRCA1/2, 2) To compare these risks with those for women diagnosed with DCIS and who do not carry mutations in BRCA1/2 and those for women not diagnosed with DCIS (controls), 3) To measure and compare the prevalence of pathologic characteristics of DCIS diagnosed in women with mutations in BRCA1/2 with those in DCIS patients without such mutations, 4) To present preliminary risk models and clinical guidelines for the management of DCIS in BRCA1/2 mutation carriers.